A Gibbs approach to Chargaff's second parity rule

Chargaff's second parity rule (CSPR) asserts that the frequencies of short polynucleotide chains are the same as those of the complementary reversed chains. Up to now, this hypothesis has only been observed empirically and there is currently no explanation for its presence in DNA strands. Here we argue that CSPR is a probabilistic consequence of the reverse complementarity between paired strands, because the Gibbs distribution associated with the chemical energy between the bonds satisfies CSPR. We develop a statistical test to study the validity of CSPR under the Gibbsian assumption and we apply it to a large set of bacterial genomes taken from the GenBank repository.Comment: 16 page

Informing investment to reduce inequalities: a modelling approach

Background: Reducing health inequalities is an important policy objective but there is limited quantitative information about the impact of specific interventions. Objectives: To provide estimates of the impact of a range of interventions on health and health inequalities. Materials and methods: Literature reviews were conducted to identify the best evidence linking interventions to mortality and hospital admissions. We examined interventions across the determinants of health: a ‘living wage’; changes to benefits, taxation and employment; active travel; tobacco taxation; smoking cessation, alcohol brief interventions, and weight management services. A model was developed to estimate mortality and years of life lost (YLL) in intervention and comparison populations over a 20-year time period following interventions delivered only in the first year. We estimated changes in inequalities using the relative index of inequality (RII). Results: Introduction of a ‘living wage’ generated the largest beneficial health impact, with modest reductions in health inequalities. Benefits increases had modest positive impacts on health and health inequalities. Income tax increases had negative impacts on population health but reduced inequalities, while council tax increases worsened both health and health inequalities. Active travel increases had minimally positive effects on population health but widened health inequalities. Increases in employment reduced inequalities only when targeted to the most deprived groups. Tobacco taxation had modestly positive impacts on health but little impact on health inequalities. Alcohol brief interventions had modestly positive impacts on health and health inequalities only when strongly socially targeted, while smoking cessation and weight-reduction programmes had minimal impacts on health and health inequalities even when socially targeted. Conclusions: Interventions have markedly different effects on mortality, hospitalisations and inequalities. The most effective (and likely cost-effective) interventions for reducing inequalities were regulatory and tax options. Interventions focused on individual agency were much less likely to impact on inequalities, even when targeted at the most deprived communities

Search based software engineering: Trends, techniques and applications

© ACM, 2012. This is the author's version of the work. It is posted here by permission of ACM for your personal use. Not for redistribution. The definitive version is available from the link below.In the past five years there has been a dramatic increase in work on Search-Based Software Engineering (SBSE), an approach to Software Engineering (SE) in which Search-Based Optimization (SBO) algorithms are used to address problems in SE. SBSE has been applied to problems throughout the SE lifecycle, from requirements and project planning to maintenance and reengineering. The approach is attractive because it offers a suite of adaptive automated and semiautomated solutions in situations typified by large complex problem spaces with multiple competing and conflicting objectives. This article provides a review and classification of literature on SBSE. The work identifies research trends and relationships between the techniques applied and the applications to which they have been applied and highlights gaps in the literature and avenues for further research.EPSRC and E

Charged pion form factor between Q2Q^2=0.60 and 2.45 GeV2^2. I. Measurements of the cross section for the 1{^1}H(e,e′π+e,e'\pi^+)nn reaction

Cross sections for the reaction ${^1}$H($e,e'\pi^+$)$n$ were measured in Hall C at Thomas Jefferson National Accelerator Facility (JLab) using the CEBAF high-intensity, continous electron beam in order to determine the charged pion form factor. Data were taken for central four-momentum transfers ranging from $Q^2$=0.60 to 2.45 GeV$^2$ at an invariant mass of the virtual photon-nucleon system of $W$=1.95 and 2.22 GeV. The measured cross sections were separated into the four structure functions $\sigma_L$, $\sigma_T$, $\sigma_{LT}$, and $\sigma_{TT}$. The various parts of the experimental setup and the analysis steps are described in detail, including the calibrations and systematic studies, which were needed to obtain high precision results. The different types of systematic uncertainties are also discussed. The results for the separated cross sections as a function of the Mandelstam variable $t$ at the different values of $Q^2$ are presented. Some global features of the data are discussed, and the data are compared with the results of some model calculations for the reaction ${^1}$H($e,e'\pi^+$)$n$.Comment: 26 pages, 23 figure

Walk well:a randomised controlled trial of a walking intervention for adults with intellectual disabilities: study protocol

Background - Walking interventions have been shown to have a positive impact on physical activity (PA) levels, health and wellbeing for adult and older adult populations. There has been very little work carried out to explore the effectiveness of walking interventions for adults with intellectual disabilities. This paper will provide details of the Walk Well intervention, designed for adults with intellectual disabilities, and a randomised controlled trial (RCT) to test its effectiveness. Methods/design - This study will adopt a RCT design, with participants allocated to the walking intervention group or a waiting list control group. The intervention consists of three PA consultations (baseline, six weeks and 12 weeks) and an individualised 12 week walking programme. A range of measures will be completed by participants at baseline, post intervention (three months from baseline) and at follow up (three months post intervention and six months from baseline). All outcome measures will be collected by a researcher who will be blinded to the study groups. The primary outcome will be steps walked per day, measured using accelerometers. Secondary outcome measures will include time spent in PA per day (across various intensity levels), time spent in sedentary behaviour per day, quality of life, self-efficacy and anthropometric measures to monitor weight change. Discussion - Since there are currently no published RCTs of walking interventions for adults with intellectual disabilities, this RCT will examine if a walking intervention can successfully increase PA, health and wellbeing of adults with intellectual disabilities

The use of therapy dogs to support court users in the waiting room

The use of animals to support individuals' wellbeing has been documented across a variety of disciplines. It has been over a decade since dogs have also started to be used within the criminal justice setting in America to support vulnerable people, but this practice is not common in the United Kingdom. Globally, empirical evidence to support the benefits of utilising dogs within the criminal justice system is lacking. The present interdisciplinary study aimed to explore one aspect of the criminal justice journey, the impact a therapy dog can have on UK court users waiting to give evidence at a magistrate's court. 117 court users and 8 court staff were interviewed to explore their perceptions of a therapy dog service offered at a local magistrates’ court. Using thematic analysis, three main themes were discovered: (1) Context of the court environment, (2) Effect of the therapy dog on well-being, and (3) Issues relating to therapy dogs in court waiting areas. Results suggests that therapy dogs have a number of benefits to court users. Long-term, the human-canine interaction positively translates into the court waiting room environment and so it should be further explored, evaluated and then appropriately implemented in the UK’s legal system

Single view silhouette fitting techniques for estimating tennis racket position

Stereo camera systems have been used to track markers attached to a racket, allowing its position to be obtained in three-dimensional (3D) space. Typically, markers are manually selected on the image plane, but this can be time-consuming. A markerless system based on one stationary camera estimating 3D racket position data is desirable for research and play. The markerless method presented in this paper relies on a set of racket silhouette views in a common reference frame captured with a calibrated camera and a silhouette of a racket captured with a camera whose relative pose is outside the common reference frame. The aim of this paper is to provide validation of these single view fitting techniques to estimate the pose of a tennis racket. This includes the development of a calibration method to provide the relative pose of a stationary camera with respect to a racket. Mean static racket position was reconstructed to within ±2 mm. Computer generated camera poses and silhouette views of a full size racket model were used to demonstrate the potential of the method to estimate 3D racket position during a simplified serve scenario. From a camera distance of 14 m, 3D racket position was estimated providing a spatial accuracy of 1.9 ± 0.14 mm, similar to recent 3D video marker tracking studies of tennis

The role of CD8+ T cell clones in immune thrombocytopenia

Immune thrombocytopenia (ITP) is traditionally considered an antibody-mediated disease. However, a number of features suggest alternative mechanisms of platelet destruction. In this study, we use a multi-dimensional approach to explore the role of cytotoxic CD8+ T cells in ITP. We characterised patients with ITP and compared them to age-matched controls using immunophenotyping, next-generation sequencing of T cell receptor (TCR) genes, single-cell RNA sequencing, and functional T cell and platelet assays. We found that adults with chronic ITP have increased polyfunctional, terminally differentiated effector memory CD8+ T cells (CD45RA+CD62L-) expressing intracellular interferon-g, tumour necrosis factor-a, and Granzyme B defining them as TEMRA cells. These TEMRA cells expand when the platelet count falls and show no evidence of physiological exhaustion. Deep sequencing of the T cell receptor showed expanded T cell clones in patients with ITP. T cell clones persisted over many years, were more prominent in patients with refractory disease, and expanded when the platelet count was low. Combined single-cell RNA and TCR sequencing of CD8+ T cells confirmed that the expanded clones are TEMRA cells. Using in vitro model systems, we show that CD8+ T cells from patients with ITP form aggregates with autologous platelets, release interferon-g and trigger platelet activation and apoptosis through TCR-mediated release of cytotoxic granules. These findings of clonally expanded CD8+ T cells causing platelet activation and apoptosis provide an antibody-independent mechanism of platelet destruction, indicating that targeting specific T-cell clones could be a novel therapeutic approach for patients with refractory ITP